BR112014032560B1 - Método para produzir a proteína iduronato-2-sulfatase (i2s) recombinante - Google Patents
Método para produzir a proteína iduronato-2-sulfatase (i2s) recombinante Download PDFInfo
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PCT/US2013/048571 WO2014005019A2 (en) | 2012-06-29 | 2013-06-28 | Cells for producing recombinant iduronate-2-sulfatase |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
WO2012045075A1 (en) | 2010-10-01 | 2012-04-05 | Jason Schrum | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
US20160145589A1 (en) | 2011-06-24 | 2016-05-26 | Green Cross Corporation | Composition and formulation comprising recombinant human iduronate-2-sulfatase and preparation method thereof |
EP4144378A1 (en) | 2011-12-16 | 2023-03-08 | ModernaTX, Inc. | Modified nucleoside, nucleotide, and nucleic acid compositions |
CA2868996A1 (en) | 2012-04-02 | 2013-10-10 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
EP3404095B1 (en) * | 2012-05-02 | 2022-07-27 | Life Technologies Corporation | High yield transient expression in mammalian cells using unique pairing of high density growth and transfection medium and expression enhancers |
US20140004097A1 (en) * | 2012-06-29 | 2014-01-02 | Shire Human Genetic Therapies, Inc. | Method of producing recombinant iduronate-2-sulfatase |
US9150841B2 (en) * | 2012-06-29 | 2015-10-06 | Shire Human Genetic Therapies, Inc. | Cells for producing recombinant iduronate-2-sulfatase |
KR101380740B1 (ko) | 2012-06-29 | 2014-04-11 | 쉐어 휴먼 제네텍 세러피스, 인코포레이티드 | 이듀로네이트-2-설파타제의 정제 |
US9512456B2 (en) | 2012-08-14 | 2016-12-06 | Modernatx, Inc. | Enzymes and polymerases for the synthesis of RNA |
PL2922554T3 (pl) | 2012-11-26 | 2022-06-20 | Modernatx, Inc. | Na zmodyfikowany na końcach |
EP2968391A1 (en) | 2013-03-13 | 2016-01-20 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
US9550972B2 (en) | 2014-09-29 | 2017-01-24 | General Electric Company | Devices, systems and methods for automated cell culturing |
EP3101125A1 (en) * | 2015-06-05 | 2016-12-07 | Laboratorios Del Dr. Esteve, S.A. | Adenoassociated virus vectors for the treatment of mucopolysaccharidoses |
JP6990176B2 (ja) | 2015-10-05 | 2022-02-03 | モデルナティエックス インコーポレイテッド | メッセンジャーリボ核酸薬物の治療投与のための方法 |
WO2019070577A1 (en) | 2017-10-02 | 2019-04-11 | Denali Therapeutics Inc. | FUSION PROTEINS COMPRISING SUBSTITUTE ENZYM THERAPY ENZYMES |
JP7060235B2 (ja) * | 2018-05-18 | 2022-04-26 | 国立大学法人広島大学 | 変異型イズロン酸-2-スルファターゼの機能回復薬剤のスクリーニング方法 |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK6488D0 (da) | 1988-01-07 | 1988-01-07 | Novo Industri As | Enzymer |
US5310646A (en) | 1988-05-13 | 1994-05-10 | Regents Of The University Of Minnesota | Method for the detection of mucopolysaccharide storage diseases |
US5932211A (en) | 1991-11-12 | 1999-08-03 | Women's And Children's Hospital | Glycosylation variants of iduronate 2-sulfatase |
WO1995024920A1 (en) | 1994-03-16 | 1995-09-21 | The Regents Of The University Of California | Treating inflammation via the administration of specific sulfatase enzymes and/or sulfation inhibitor |
US5863782A (en) | 1995-04-19 | 1999-01-26 | Women's And Children's Hospital | Synthetic mammalian sulphamidase and genetic sequences encoding same |
DE19527054A1 (de) | 1995-07-26 | 1997-01-30 | Behringwerke Ag | Verfahren zur Charakterisierung der Glycosylierung von Glycoproteinen sowie zur in-vitro Bestimmung der Bioverfügbarkeit von Glycoproteinen |
EP2221361A3 (en) | 1996-08-30 | 2011-02-09 | Life Technologies Corporation | Method for producing a polypeptide in vitro in mammalian cells in a protein-free and serum-free culture medium |
US7368531B2 (en) | 1997-03-07 | 2008-05-06 | Human Genome Sciences, Inc. | Human secreted proteins |
US7083793B2 (en) | 1999-02-26 | 2006-08-01 | Millennium Pharmaceuticals, Inc. | Tango 243 polypeptides and uses thereof |
WO2000050443A2 (en) | 1999-02-26 | 2000-08-31 | Millennium Pharmaceutcals, Inc. | Secreted proteins and uses thereof |
DK1171615T3 (da) | 1999-04-26 | 2007-03-19 | Genentech Inc | Celledyrkningsfremgangsmåde for glycoproteiner |
JP2002017376A (ja) | 1999-07-08 | 2002-01-22 | Herikkusu Kenkyusho:Kk | 分泌蛋白質、または膜蛋白質 |
CA2383800A1 (en) | 1999-09-03 | 2001-03-15 | Human Genome Sciences Inc. | 52 human secreted proteins |
US6780627B1 (en) | 2000-01-31 | 2004-08-24 | Millennium Pharmaceuticals, Inc. | 22438, 23553, 25278, and 26212 novel human sulfatases |
AU2001238488A1 (en) | 2000-02-17 | 2001-08-27 | Incyte Genomics, Inc. | Human kinases |
EP1268541A1 (en) | 2000-03-17 | 2003-01-02 | Human Genome Sciences, Inc. | 7 human ovarian and ovarian cancer associated proteins |
ES2484966T3 (es) | 2000-04-12 | 2014-08-12 | Novozymes Biopharma Dk A/S | Proteínas de fusión de albúmina |
US20030148920A1 (en) | 2000-12-27 | 2003-08-07 | Steven Rosen | Sulfatases and methods of use thereof |
WO2002098455A2 (en) | 2001-06-07 | 2002-12-12 | Hemebiotech A/S | Production of recombinant human arylsulfatase a |
US20060234226A1 (en) | 2002-04-26 | 2006-10-19 | Fahner Robert L | Non-affinity purification of proteins |
US6890736B1 (en) | 2002-09-20 | 2005-05-10 | Immunex Corporation | Methods for producing proteins in cultured cells |
TWI312368B (en) | 2002-12-23 | 2009-07-21 | Bristol Myers Squibb Compan | Mammalian cell culture processes for protein production |
CN1759176B (zh) * | 2003-02-11 | 2012-10-03 | 夏尔人类遗传性治疗公司 | 使用甲酰-甘氨酸生成酶(fge)对多种硫酸酯酶缺乏症和其它病症进行诊断和治疗 |
US20050019914A1 (en) | 2003-07-24 | 2005-01-27 | Aventis Pharma Deutschland Gmbh | Perfusion process for producing erythropoietin |
WO2005113765A2 (en) | 2004-05-06 | 2005-12-01 | Biomarin Pharmaceutical Inc. | Methods of activation of sulfatases and methods and compositions of using the same |
CA2609060C (en) | 2005-06-03 | 2014-07-15 | Urs Weber | Production of recombinant il-18 binding protein |
CN101437839A (zh) | 2006-03-20 | 2009-05-20 | 米德列斯公司 | 蛋白质纯化 |
WO2009091994A2 (en) | 2008-01-18 | 2009-07-23 | Biomarin Pharmaceutical Inc. | Manufacture of active highly phosphorylated human lysosomal sulfatase enzymes and uses thereof |
CN105664811B (zh) * | 2009-10-09 | 2018-10-09 | 蓝立方知识产权公司 | 生产氯化和/或氟化丙烯和高级烯烃的绝热活塞流反应器及方法 |
EP2485761B1 (en) | 2009-10-09 | 2019-02-27 | Armagen, Inc. | Methods and compositions for increasing iduronate 2-sulfatase activity in the cns |
WO2011108451A1 (ja) | 2010-03-01 | 2011-09-09 | 日本ケミカルリサーチ株式会社 | 遺伝子ノックアウト細胞を用いた組換え体リソソーム酵素の製造方法 |
KR102356192B1 (ko) | 2010-06-25 | 2022-02-08 | 샤이어 휴먼 지네틱 테라피즈 인크. | 이듀로네이트-2-설파타제의 cns 전달을 위한 방법들 및 조성물들 |
WO2012101671A1 (en) | 2011-01-25 | 2012-08-02 | Jcr Pharmaceuticals Co., Ltd. | Method for production of human recombinant iduronate 2-sulfatase |
KR101158673B1 (ko) | 2011-06-24 | 2012-07-03 | 주식회사 지씨바이오 | 재조합 인간 이듀로네이트-2-설파타아제를 포함하는 조성물, 제제 및 이의 제조방법 |
KR101380740B1 (ko) | 2012-06-29 | 2014-04-11 | 쉐어 휴먼 제네텍 세러피스, 인코포레이티드 | 이듀로네이트-2-설파타제의 정제 |
US9150841B2 (en) | 2012-06-29 | 2015-10-06 | Shire Human Genetic Therapies, Inc. | Cells for producing recombinant iduronate-2-sulfatase |
US20140004097A1 (en) | 2012-06-29 | 2014-01-02 | Shire Human Genetic Therapies, Inc. | Method of producing recombinant iduronate-2-sulfatase |
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